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Sevoflurane remifentanil interaction: comparison of different response surface models

Bjorn Heyse, Johannes H Proost, Peter M Schumacher, Tomas W Bouillon, Hugo EM Vereecke, Douglas J Eleveld, Martin Luginbuhl and Michel Struys UGent (2012) ANESTHESIOLOGY. 116(2). p.311-323
abstract
Background: Various pharmacodynamic response surface models have been developed to quantitatively describe the relationship between two or more drug concentrations with their combined clinical effect. We examined the interaction of remifentanil and sevoflurane on the probability of tolerance to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy in patients to compare the performance of five different response surface models. Methods: Forty patients preoperatively received different combined concentrations of remifentanil (0-12 ng/ml) and sevoflurane (0.5-3.5 vol.%) according to a criss-cross design (160 concentration pairs, four per patient). After having reached pseudosteady state, the response to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy was recorded. For the analysis of the probability of tolerance, five different interaction models were tested: Greco, Reduced Greco, Minto, Scaled C50(O) Hierarchical, and Fixed C50(O) Hierarchical model. All calculations were performed with NONMEM VI (Icon Development Solutions, Ellicott City, MD). Results: The pharmacodynamic interaction between sevoflurane and remifentanil was strongly synergistic for both the hypnotic and the analgesic components of anesthesia. The Greco model did not result in plausible parameter estimates. The Fixed C50(O) Hierarchical model performed slightly better than the Scaled C50(O) Hierarchical and Reduced Greco models, whereas the Minto model fitted less well. Conclusion: We showed the importance of exploring various surface model approaches when studying drug interactions. The Fixed C50(O) Hierarchical model fits our data on sevoflurane remifentanil interaction best and appears to be an appropriate model for use in hypnotic-opioid drug interaction.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ALVEOLAR CONCENTRATION, PHARMACOKINETICS, ISOFLURANE, FENTANYL, REQUIREMENTS, REDUCTION, MIDAZOLAM, INCISION, PROPOFOL, PHARMACODYNAMICS
journal title
ANESTHESIOLOGY
Anesthesiology
volume
116
issue
2
pages
311 - 323
Web of Science type
Article
Web of Science id
000299666200011
JCR category
ANESTHESIOLOGY
JCR impact factor
5.163 (2012)
JCR rank
2/29 (2012)
JCR quartile
1 (2012)
ISSN
0003-3022
DOI
10.1097/ALN.0b013e318242a2ec
language
English
UGent publication?
yes
classification
A1
additional info
This article is accompanied by an editorial view: see Shafer SL, All models are wrong, Anesthesiology 2012; 116(2):240-1, DOI 10.1097/ALN.0b013e31824234c5
copyright statement
I have transferred the copyright for this publication to the publisher
id
2075133
handle
http://hdl.handle.net/1854/LU-2075133
date created
2012-03-27 14:23:50
date last changed
2016-12-19 15:44:51
@article{2075133,
  abstract     = {Background: Various pharmacodynamic response surface models have been developed to quantitatively describe the relationship between two or more drug concentrations with their combined clinical effect. We examined the interaction of remifentanil and sevoflurane on the probability of tolerance to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy in patients to compare the performance of five different response surface models. 
Methods: Forty patients preoperatively received different combined concentrations of remifentanil (0-12 ng/ml) and sevoflurane (0.5-3.5 vol.\%) according to a criss-cross design (160 concentration pairs, four per patient). After having reached pseudosteady state, the response to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy was recorded. For the analysis of the probability of tolerance, five different interaction models were tested: Greco, Reduced Greco, Minto, Scaled C50(O) Hierarchical, and Fixed C50(O) Hierarchical model. All calculations were performed with NONMEM VI (Icon Development Solutions, Ellicott City, MD). 
Results: The pharmacodynamic interaction between sevoflurane and remifentanil was strongly synergistic for both the hypnotic and the analgesic components of anesthesia. The Greco model did not result in plausible parameter estimates. The Fixed C50(O) Hierarchical model performed slightly better than the Scaled C50(O) Hierarchical and Reduced Greco models, whereas the Minto model fitted less well. 
Conclusion: We showed the importance of exploring various surface model approaches when studying drug interactions. The Fixed C50(O) Hierarchical model fits our data on sevoflurane remifentanil interaction best and appears to be an appropriate model for use in hypnotic-opioid drug interaction.},
  author       = {Heyse, Bjorn and Proost, Johannes H and Schumacher, Peter M and Bouillon, Tomas W and Vereecke, Hugo EM and Eleveld, Douglas J and Luginbuhl, Martin and Struys, Michel},
  issn         = {0003-3022},
  journal      = {ANESTHESIOLOGY},
  keyword      = {ALVEOLAR CONCENTRATION,PHARMACOKINETICS,ISOFLURANE,FENTANYL,REQUIREMENTS,REDUCTION,MIDAZOLAM,INCISION,PROPOFOL,PHARMACODYNAMICS},
  language     = {eng},
  number       = {2},
  pages        = {311--323},
  title        = {Sevoflurane remifentanil interaction: comparison of different response surface models},
  url          = {http://dx.doi.org/10.1097/ALN.0b013e318242a2ec},
  volume       = {116},
  year         = {2012},
}

Chicago
HEYSE, BJORN, Johannes H Proost, Peter M Schumacher, Tomas W Bouillon, Hugo EM Vereecke, Douglas J Eleveld, Martin Luginbuhl, and Michel Struys. 2012. “Sevoflurane Remifentanil Interaction: Comparison of Different Response Surface Models.” Anesthesiology 116 (2): 311–323.
APA
HEYSE, B., Proost, J. H., Schumacher, P. M., Bouillon, T. W., Vereecke, H. E., Eleveld, D. J., Luginbuhl, M., et al. (2012). Sevoflurane remifentanil interaction: comparison of different response surface models. ANESTHESIOLOGY, 116(2), 311–323.
Vancouver
1.
HEYSE B, Proost JH, Schumacher PM, Bouillon TW, Vereecke HE, Eleveld DJ, et al. Sevoflurane remifentanil interaction: comparison of different response surface models. ANESTHESIOLOGY. 2012;116(2):311–23.
MLA
HEYSE, BJORN, Johannes H Proost, Peter M Schumacher, et al. “Sevoflurane Remifentanil Interaction: Comparison of Different Response Surface Models.” ANESTHESIOLOGY 116.2 (2012): 311–323. Print.